RNA interference (RNAi) agents and the use of the RNAi agents for treating hepatitis B infection in individuals, as well as pharmaceutical compositions containing the RNAi agents are provided. The RNAi agents, or constructs for expressing them are utilized to inhibit expression of at least one Hepatitis B virus (HBV) gene, wherein each agent comprises an effector sequence complementary to or substantially complementary to a predicted sequence transcribed from a target region. In some embodiments of the present invention, the agents have more than one effector sequence; wherein the multiple effectors may target the same region of an HBV gene, different (possibly overlapping) regions of the same gene and/or different HBV genes.